1. Field of the Invention
This invention relates to prostaglandin precursors and processes for preparing the same. More particularly, this invention relates to 6-alkenyl-bicyclo[3.1.0]hexanone compounds represented by the formula (I) hereinafter described and cyclopentanone compounds represented by the formula (II) hereinafter described which are useful as precursors for the synthesis of prostaglandin derivatives, and processes for preparing such prostaglandin precursors.
2. Description of the Prior Art
It is well known that the naturally-occurring prostaglandin compounds are composed of 20 carbon atoms and contain in the structure thereof a cyclopentanone ring and exist broadly in the brain, lung, kidney semen, uterus membrane, etc. of living body. These prostaglandin compounds are also known to have a wide variety of excellent pharmacological activities such as anti-ulcer, hypotensive, anti-asthmatic, uterotonic activities depending upon critical differences in the chemical structure of prostaglandin compounds, and recently the synthesis of prostaglandin compounds has been extensively studied.
Hitherto, in the synthesis of prostaglandin derivatives, the basic cyclopentanone structure is typically formed by (1) a method utilizing Dieckmann reaction as described, for example, in P. S. Pinkney, Or. Synthesis,Coll. Voll., 2, 116 (1943), (2) a method by Claisen condensation of 1,4-dicarbonyl compounds as described, for example, in R. A. Elison, Synthesis, 397 (1973) and (3) a method starting with cyclopentadiene as decribed, for example, in E. J. Corey et al., J. Amer. Chem. Soc. 93, 1489 (1971).
On the other hand, some of the conventional methods for the synthesis of prostaglandin derivatives employs a bicyclo[3.1.0]hexane compound as an intermediate as described, for example, in W. P Schneider, Chem. Commun., 304 (1969) and E. J. Corey et al., J. Amer. Chem. Soc., 94, 4014 (1972), but these methods are not considered to be practically useful since the ring-opening of the cyclopropane moiety contained in the above bicyclo[3.1.0]hexane compound takes place only in a low yield and the resulting compound is usually a mixture of diastereomers.
As is well known in the art, the basic structure of prostaglandin derivatives is composed of a cyclopentanone nucleus substituted with an alkyl group or an alkenyl group at the 2- or 3-position of the cyclopentanone nucleus. These side chains were conventionally introduced during the synthesis of prostaglandin derivatives.
More specifically, typical conventional procedures for introducing a side chain at the 3-position of the cyclopentanone nucleus comprise introducing an alkyl or alkenyl group by Michael type addition reaction, as described in C. J. Sih, et al., J. Amer. Chem. Soc., 94, 3643 (1972), and J. H. Fried, J. Amer. Chem. Soc., 94, 9256 (1972), or by reacting a carbonyl group contained in the substituent at the 3-position with a carbon anion to extend a chain length utilizing a carbon-carbon extension reaction, for example, by Wittig reaction, as described in E. J. Corey et al., J. Amer. Chem. Soc., 91, 5675 (1969).
Each of the above conventional processes has certain characteristic features, but is not considered advantageous procedures from the standpoint that it requires expensive and/or dangerous reagents, critical reaction doncditions which are very difficult to be controlled, and isolation and purification of the desired product with considerable difficulty, and that the process generally has low selectivity of reaction thereby resulting in low yield of the desired product.
Further, it is well known that 3-(3'-hydroxy-1'-alkenyl)-cyclopentanone-2-carboxylic acid esters represented by the formula (IV) hereinafter described are useful as precursors for the synthesis of certain types of prostaglandin compounds (PGA.sub.2) as described in, for example, J. Martel et al., Tetrahedron Lett., 1972, 149. The above 3-(3'-hydroxy-1'-alkenyl)cyclopentanone-2-carboxylic acid esters were conventionally prepared by intramolecular ring-opening reaction of vinyl-substituted epoxide compounds, but the synthesis of these epoxide compounds requires many reaction steps and, therefore, developments on more expedient and economical methods for producing the 3-(3'-hydroxy-1'-alkenyl)cyclopentanone-2-carboxylic acid esters have been strongly desired from the standpoint of the production of prostaglandin compounds on an industrial scale.
Recently, various methods for the synthesis of prostaglandin compounds have been developed, and one of the methods comprises rearrangement reaction of cyclopentanone sulfoxide compounds represented by the formula (IId) hereinafter described in the presence of a reagent having a thiophilicity, as described in G. Stork et al., J. Amer. Chem. Soc., 96, 6774 (1974). However, the method for the synthesis of the above cyclopentanone sulfoxide compounds used as precursors in the above rearrangement reaction taught in the above reference is not considered to be advantageous since this method requires various reaction steps, expensive reagents and very critical reaction conditions.